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我不是醫師,更不懂化療、電療,只是一個普通的二期癌症病人,卻因為採用我自己認為對的方法,迅速治癒癌症,感謝主!!!!

 
Journal of Nutritional & Environmental Medicine
營養與環境醫學期刊

Month 2008; 000(000): 000–000

ORIGINAL ARTICLE

原版資料

Pharmacokinetics of oral vitamin C

口服維生素C藥代動力學

作者:STEPHEN HICKEY1,2, HILARY J. ROBERTS3, & NICHOLAS J. MILLER4

Faculty of Computing, Engineering and Technology, Staffordshire University, Staffordshire, UK,

作者:分別任職於:斯塔福德郡大學計算機工程與技術學院,英國斯塔福德郡

2 School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester

英國曼徹斯特曼徹斯特大都會大學生物學與化學與健康科學學院

Freelance scientific writer, and 4Biolab Medical Unit, London, UK

自由業科學論述家,以及英國倫敦的4個生物實驗室。

Abstract

摘要

Purpose. To test whether plasma vitamin C levels, following oral doses in supplemented volunteers, are tightly controlled and subject to a maximum in the region of 220 um/L, as suggested by previous researchers for depleted subjects. To determine plasma levels following single, variable-sized doses of standard and liposomal formulations of vitamin C and compare the effects of the different formulations.

目的:以志願者,實施口服劑後的血漿維生素C濃度測試,過程中受到嚴格控制,如以往研究人員的建議,希望能達到前研究人員所獲得的最大值220 um/L之範圍。並確定實施口服單一或不同劑量維生素C和脂質性維生素C,對血漿濃度會產生的數據變化,並比較不同劑量配方的效果。

To determine whether plasma levels above ,280 um/L, which have selectively killed cancer, bacteria or viruses (in laboratory experiments), can be achieved using oral doses of vitamin C.

用以確定使用口服劑的維生素C可以實現高於280um / L的血漿濃度,因這種濃度,可以殺死癌症,細菌或病毒(在實驗室實驗中)。

Design. This was a single blind study, measuring plasma levels in two subjects, in samples taken half-hourly or hourly for 6 hours, following ingestion of vitamin C.

設計: 這是一項單盲研究,測量兩個受試者攝取維生素C後,半小時或以小時為單位,持續6小時的血漿濃度。

Data were compared with published results and with data from 10 years of laboratory plasma determinations.

獲得之數據將與來自最近10年實驗室公佈的血漿數據進行比較

Materials and methods. Standard 1 gram tablets of vitamin C; liposomal vitamin C. Plasma levels were analysed using the method of Butts and Mulvihill.

材料和方法: 標準1克維生素C; 脂質體維生素C。使用ButtsMulvihill方法來分析血漿濃度。

Results. Preliminary investigations of the effects of liposomal and standard formulation ascorbate showed that blood plasma levels in excess of the previously assumed maximum of 220 um/L are possible. Large oral doses of liposomal ascorbate resulted in plasma levels above 400 um/L.

結果:對脂質體和標準抗壞血酸鹽製劑初步研究的數據證明,超過先前假定的最大值220um / L的血漿濃度是可能的。大量口服脂質體抗壞血酸鹽能導致血漿濃度高於400um / L

Conclusions. Since a single oral dose can produce plasma levels in excess of 400 um/L,pharmacokinetic theory suggests that repeated doses could sustain levels well above the formerly

assumed maximum.

結論:單次的口服劑量就可以產生超過400um / L的血漿濃度,藥代動力學理論表明,若重複實施口服,可以維持遠高於以前假定最大的濃度。

These results have implications for the use of ascorbate, as a nutrient and as a drug. For example, a short in vitro treatment of human Burkitt’s lymphoma cells with ascorbate, at 400 um/L, has been shown to result in ,50% cancer cell death. Using frequent oral doses, an equivalent plasma level could be sustained indefinitely.

這些結果對於使用抗壞血酸(就是我們在義大癌醫院靜脈注射的高劑量維他命C),不論是作為營養品或是藥物都會產生影響。例如,已經證實使用400um / L的抗壞血酸,對人類伯基特淋巴癌細胞的短暫時間的體外治療就可導致50%的癌細胞死亡而且只要使用多次的口服,就可以無限期地維持相同的抗壞血酸在血漿中的濃度。

Thus, oral vitamin C has potential for use as a non-toxic, sustainable, therapeutic agent. Further research into the experimental and therapeutic aspects of high, frequent, oral doses of ascorbic acid either alone or (for cancer therapy) in combination with synergistic substances, such as alpha-lipoic acid, copper or vitamin K3, is needed urgently.

因此,口服維生素C具有無毒,而且擁有可持續的當作治療劑運用的潛力。迫切的需要進一步研究濃度更高、服用次數更多、單獨口服或是用於癌症治療時,配合其他藥物如α-硫辛酸,銅或維生素K3的組合的實驗。

Key words: Vitamin C, ascorbic acid, nutrition, liposomes, cancer, pharmacokinetics

關鍵詞:維生素C,抗壞血酸,營養,脂質體,癌症,藥代動力學

Introduction

The amount of vitamin C required for good health represents a challenging aspect of scientific nutrition. Although authorities agree that a few milligrams of ascorbate will prevent acute scurvy, estimates of the optimal intake vary widely. Various experts have

proposed doses, ranging from ,40 milligrams [1] to several grams a day [2]: a difference more than 100-fold. The debate has been vigorous, especially since Linus Pauling popularized the hypothesis of higher dose requirements.

介紹

在健康方面,對維生素C需要的量,一直是營養科學的一個具有挑戰性的課題。雖然主管當局同意,給與幾毫克的抗壞血酸就可以預防嚴重的壞血病,但對在最佳攝入量的估計,卻有很大差異。各個專家都有提出自己的劑量需要,範圍從40毫克[1]到幾克/[2]:差異超過100倍。引發激烈的爭論,特別是Linus Pauling醫師倡導下,提出高劑量維生素C的假設。

In an attempt to set vitamin C requirements on a more rigorous scientific basis, the National Institutes of Health (NIH) conducted a series of pharmacokinetic depletion andrepletion experiments. These studies were based on seven male [3] and 15 female [4] young, adult subjects [5]. Results indicated that the kidney selectively retains a minimum plasma level of ,70 um/L; which varies slightly among subjects.

在科學基礎上,為了更加嚴格的設定維生素C劑量的需求,美國國家衛生研究院(NIH)進行了一系列藥代動力學消耗和補充實驗。這些研究以年輕成人為受試者,包含7名男性[3]15名女性[4] [5]。結果顯示,選擇在腎臟能保留70um / L的最小血漿濃度; 每位受測人之間略有不同。

This baseline is protected by ascorbate re-uptake pumps in the kidney, leading to an excretion half-life of 8–40 days, for low (sub-baseline) levels of vitamin C [6].

該實驗的基準,是由腎臟中的抗壞血酸鹽再吸收泵來實施保護,經過8-40天排泄半衰期後,還能維持低(次基線)維生素C濃度。

Single, daily 200mg doses of vitamin C were shown to maintain this baseline plasma concentration at what the NIH described as a maximal (or ‘saturation’) level [4,5]. The NIH reported that single doses higher than ,200mg did not substantially increase the baseline level, which appeared to be limited by the capacity of the re-uptake transporters.

NIH的敘述是以單次服用,每日200mg維生素C劑量,就已經是最大(或"飽和度")且能維持血漿的濃度[4,5] NIH報告又說,高於200mg的劑量基本上是無法持續或增加的,這明顯受到再攝取能力的限制。

The NIH data shows that single, higher, oral doses (up to 1250 mg) raise plasma levels transiently.

NIH數據顯示,單次,以更高的口服劑量(高達1250mg)僅能做到瞬時升高血漿濃度。

The shape of the vitamin C response curve results primarily from the rate of oral absorption, combined with an excretion half-life of ,30 minutes. A secondary effect concerns its absorption and release from body tissue compartments.

維生素C反應曲線的形狀,主要影響是來自口服後吸收的速率,加上30分鐘的排泄半衰期作用。其次是來自身體器官的吸收力和釋放力。

Oral absorption of vitamin C is a two-phase, non-linear process; bodily levels are dependent on current intakes. Low intakes produce plasma levels below ,70 um/L, with a long-half life,

consistent with resistance to acute scurvy [7]. Higher single doses produce transient increases in plasma concentration, which the NIH group predicted to be limited to a maximum of 220 um/L [8].

維生素C的口服吸收力是分兩階段、非線性過程; 體內濃度取決於目前的攝入量。低攝入量會產生低於70um / L的血漿,半衰期長,此特質與抗急性壞血病現象一致[7]。高的單次劑量會產生血漿濃度的瞬時增加,NIH他們預計最大濃度為220um / L [8]

Continuous supplementation, in combination with specific administration technologies,can produce levels greater than the NIH prediction. Here, we provide evidence that plasma levels following oral administration of liposomal ascorbate can reach approximately twice the predicted maximum. These findings have previously unrealized implications for the use of oral vitamin C as a therapeutic agent for various diseases, including cancer.

但我們卻能提供證據,連續的服食,結合特定的管理,可以產生比NIH預測更高的濃度。在這裡,我們已證實口服脂質體維生素C後的血漿濃度可達到預期最大值的兩倍。這些發現是以前未料想到的,使用口服維生素C就可以對包括癌症在內的多種疾病,產生治療功效

Methods

Ethical approval for the study was obtained from the ethics committee at Manchester Metropolitan University and the UK Department of Health. Two subjects, one female (52) and one male (55), had previously taken a minimum of 6 grams per day of vitamin C and an average exceeding 10 grams per day, in divided doses, for a period of 12 months.

方法

本研究關於倫理方面層次,已由曼徹斯特城市大學和英國衛生部的倫理委員會獲得批准。兩名受試者,一名女性(52)和一名男性(55),他們過去曾經每天服用維生素C至少6克,平均每天服用量超過10克,兩人是分開服用,為期12個月。

Both subjects had apparently normal renal function, with no history of kidney stones or renal disease. At the start of the study, each subject fasted for 12 hours, with no intake of vitamin

C before the first (background) measurement. This interval was chosen to ensure almost complete return of the plasma level to baseline, consistent with published pharmacokinetic data [4,5,8] and known absorption and excretion characteristics [9].

兩名受試者腎功能均明顯正常,無腎結石或腎臟疾病史。在研究開始時,每個受試者先空腹12小時,在開始測量之前不准攝取維生素C。這段時間間隔,用以確保血漿濃度幾乎完全恢復到基準值,這與公佈的藥代動力學數據[4,5,8]和已知的吸收與排泄特性,保持一致[9]

On three sequential mornings, a nurse drew a background blood sample from each subject. Immediately after this, the subjects consumed single 5, 20 or 36 gram doses of vitamin C, in a liposomally encapsulated formulation. Control measurements employed 5 gram doses of a standard ascorbic acid tablet (Table I). The dosing procedure was single blind: neither nurses nor biochemists were aware of the dose taken. Subsequently, blood

samples were taken at half-hourly or hourly intervals by individual venipunctures, to avoid the use of anticoagulants.

連續三個上午,護士從每個受試者先抽取血樣。隨後,受試者服食脂質體維生素C,服食劑量為5,2036克。管制方式是引用攝取5克劑量的標準抗壞血酸片表(表I)。給藥程序是單盲的:護士和生化師都不知道服用的劑量。 隨後,使用靜脈穿刺以半小時或一小時間隔採集血液樣品,並避免使用抗凝血劑。

The standard commercial preparation of vitamin C employed nominally 1 gram tablets with bioflavonoids (Holland and Barrett, Nuneaton, UK). This provides a comparison with existing formulations, since the short-term plasma response to oral ascorbic acid has been quantified previously [4,5,10].

使用一般商業製作標準化的維生素C,名義上是使用生物類黃酮1克片劑(HollandBarrettNuneatonUK)。本實驗提供了與現有對口服抗壞血酸的短期血漿反應[4,5,10]資料的比較。

The response to these doses was compared with published

pharmacokinetic responses to oral doses of ascorbic acid. In addition, one author (NM) had access to the results of plasma ascorbate measurements from Biolab Laboratories.

最後,我們會將這些劑量的反應所獲取之資料與已發表的對口服抗壞血酸劑量的藥代動力學反應數據實施比較,此外,還允許一位採訪者(NM)來採訪Biolab Laboratories的血漿抗壞血酸測量之結果。

Biolab has made plasma measurements since 1984 and NM has made ,30 plasma determinations per week (1500 per year) since 1997; overall ,15 000 measurements.

1984年以來Biolab每週實施30次血漿測量(每年1500次);1997年以來,他們一共實施過15 000次的測量。

The liposomal formulation employed nominally 1-gram doses, encapsulated in phosphatidylcholine liposomes (Livon Laboratories, Henderson, NV). The liposomal vitamin C was subject to an external high performance liquid chromatography (HPLC:

Varian ProStar PDA) validation, which measured 1055 mg of ascorbate per (1 g) sachet.

脂質體製劑方面,我們採用1克劑量,它包封在磷脂酰膽鹼脂質體(Livon LaboratoriesHendersonNV)中。並將脂質體維生素C進行外部高效液相色譜(HPLCVarian ProStar PDA)檢驗,測量到每小包脂質體維生素C1克)含有1055mg抗壞血酸

The measured pH was 6, consistent with the fact that the liposomes contained vitamin C in a salt form, sodium ascorbate.

Blood plasma measurements were obtained over the first 6 hours of absorption.

測量其pH6,脂質體的維生素C也屬於鹽的形式,證實與抗壞血酸鈉是一致的。並在服用6小時內測量血漿的吸收情形。

Plasma vitamin C was measured by the method of Butts and Mulvihill [11], adapted for the Cobas Mira analyser (F. Hoffman-La Roche Ltd., Diagnostics Division, CH–4002, Switzerland).

The technique depends on reduction of ferric to ferrous ions by ascorbate, which is simultaneously converted to dehydroascorbate. This method had been calibrated against the 2,4-DNPH method [12] and the fluorimetric method [12].

測量血漿維生素C是使用ButtsMulvihill [11]的方法,此法是適用於Cobas Mira分析儀(F. Hoffman-La Roche Ltd.Diagnostics DivisionCH-4002Switzerland)。該方法已經針對2,4-DNPH [12]和螢光法[12]實施過校準。該項技術是將抗壞血酸還原為亞鐵離子,並同時轉化為脫氫抗壞血酸。

Calibration standards were freshly prepared for each analytical run and three different control samples were included with each batch of samples, giving a between-batch coefficient of variation of ,3%.

儀器的校準標準如下:每次分析樣品前,均重新清理歸零,再開始測試。每批測試樣品,都包含三個不同的受管制樣品,測試批次之間允許有3%變異數。

We analysed the data using standard pattern recognition techniques [13] in terms of outlier determination [14,15] and computed the probability that the z-value of an observed

pattern was consistent with a normal distribution of values by direct numerical integration, using Simpson’s method [16].

我們使用標準圖型識別技術[13],以異常值確定[14,15]來分析數據,併使用Simpson的方法,計算出的Z值概率的圖形,此與直接以計算數值積分的常態分佈是一致的。

Results

The Biolab plasma ascorbate measurements are entirely consistent with the reference interval of 34–114 um/L [17], which corresponds to the 95% interfractile interval of the population studied. Approximately 2.5% of values are below that reference interval and 2.5% are above the reference interval. Biolab’s lowest recorded value for serum vitamin C was 8.0 um/L, at which level the subject was in danger of entering acute scurvy. Of the

15 000 measurements, the highest recorded serum value in a subject not receiving intravenous vitamin C was 220 um/L.

結果

Biolab做出的等離子體抗壞血酸測量出來的數據,都在34-114um / L的參考範圍值內[17] 95%數據是符合以前研究人員所提供的資料。大約有2.5%的數據低於參考區間,也有2.5%高於參考區間。Biolab血清維生素C的最低記錄值為8.0um / L,在該濃度下,受試者有發生急性壞血病的危險。在15 000次測量中,未接受靜脈注射維生素C的血液濃度最高記錄為220um / L

This is consistent with the published maximum value. With intravenous administration, Biolab have recorded plasma values in excess of 5000 um/L, in subjects under ascorbate treatment for osteosarcoma.

這與已公布的最大值是一致。透過靜脈注射,Biolab曾在骨肉瘤抗壞血酸治療受試者中,出現過血漿濃度超過5000um / L的數值。

Baseline levels in the two long-term supplemented subjects, measured at the start of each day, ranged from 100–150 um/L. The subjects were thus consistently in the short elimination half-life phase of plasma response.

對這兩位長期服食維生素C的受試對象,開始測量以後,每天實施測量的血漿的基準濃度範圍為100-150um / L。因此受試者一直處於血漿反應的短消除半衰期階段。

Figure 1 shows the response of the female subject to single 5 g doses of liposomal and standard formulation vitamin C; both produced similar response curves. These results are comparable in form and magnitude to those expected for oral vitamin C in previously depleted subjects. However, peak values exceeded 220 um/L, which has been reported as the maximum value attainable with repeated oral doses of 3 g six times daily [8].

1顯示了女性受試者對單次給與5 g劑量的脂質體和標準製劑維生素C的反應;兩者產生類似的反應曲線。這些結果不論形式和數值上與以前受試者攝取維生素C預期的結果相似。然而,最高值卻超過220um / L,我們認為是因每天6次重複攝取劑量的因素,才達到這最大值[8]

The subjects were experienced users of high-dose vitamin C and neither suffered any gastrointestinal effects at this dose level.

Increasing the dose of liposomal vitamin C to 20 g gave a broader response, with a delayed maximum, as shown in Figure 2. In this graph, the 20 g liposomal dose is compared with a 5 g standard dose (male subject).

因受試者是攝取高劑量維生素C經驗豐富的人,在該劑量濃度下,沒有發生任何胃腸道的不適。如圖2所示,將脂質體維生素C的劑量增加到20g,產生了更廣的反應與最大的延續時間。在圖2中,已將20g脂質體劑量與5g標準劑量(男性受試者)進行比較。

With a 20 g intake, the peak plasma level was delayed and the response was broader, indicating a greater absorption of vitamin C. The 5 g data set shows a marked outlier (peak): this is attributed to the fact that one of the (5 g) blood samples was difficult to extract, with inflammation at the puncture site, providing only a small sample.

The subject experienced no bowel tolerance effects at either of these intakes.

當攝入量為20 g時,血漿濃度的峰值發生延緩,反應更寬,表示維生素C吸收更多。5g的數據,顯示出有明顯的異常值(峰值):這是由於(5 g)血液樣本在穿刺部位有發炎,所以僅提供小量的樣本。

在這些攝入量中,受試者沒有發現腸道耐受性發生影響。

Figure 3 shows plasma levels following a 36 g dose of liposomal vitamin C, for both subjects. This resulted in peak plasma levels, in the region of 400 um/L. A 95% interfractile range (34–114), which contains 95% of the distribution with a mean of 74 corresponds to a calculated standard deviation of 17.4. We note that, under these conditions, an outlier measurement of 400 um/L would correspond to a deviation of 10.3 s with a theoretical

p-value of 1.6610213 (i.e. p,0.000 000 000 000 1). With this high dose, both subjects exceeded their bowel tolerance, leading to diarrhoea. This intolerance presumably arose from the high intake of phospholipid, without food buffering, in fasting individuals.

3顯示了對於兩位受試者,攝取36g劑量的脂質體維生素C的血漿濃度。其峰值血漿濃度,到達400um / L的區域。在95%資料的範圍內(34-114),平均值為74,對應於計算的標準差17.4。我們注意到,在這些條件下,測量400um / L的異常值,保持在理論上的偏差值10.3sp值為1.6610213(亦即p0.000 000 000 000 1)。在這個高劑量下,兩個受試者都超過腸道的耐受度,發生腹瀉。這個不耐受性原因,大概來自於磷脂的攝入量偏高,而且事先無進食食物填肚子做緩衝。

再將英國STEPHEN等四人對脂C的抗癌研究報告...重點分析一下

A.當一次空腹服用脂C 20克,2.5小時後開始,血液C的濃度達到300um/L,能維持3.5小時左右,這個C濃度對淋巴癌體外觀測是:一小時就能死亡30%

B.當一次空腹服用脂C 36克,2小時後開始,血液C的濃度達到300um/L,能維持7.9小時左右,這個濃度對淋巴癌體外觀測:一小時就能死亡30%

吃完後4.8小時,血液C的濃度攀升到400 um/L,能維持2小時,這種C濃度對淋巴癌體外觀測是:一小時就能死亡50%

However, our observations using hourly doses suggest that daily intakes of this magnitude are tolerable without bowel effects, as long as the dose is spread throughout the day.

但是,我們曾以小時為單位的不斷觀察,攝取這種高劑量的實驗結果,發現這種攝入的高劑量方式,不會影響腸道不適,是可接受的。

Discussion

This is the first published report of the effects of a liposomal formulation on the absorption of vitamin C. This preliminary study covers two subjects, which is ,10% of the number used by the NIH to recommend a dietary allowance for the general population. While

results from two subjects do not provide an indication of the underlying biodiversity, they demonstrate that previous expectations for vitamin C plasma levels may have been based on a restricted sample of depleted individuals and do not likely cover the range of responses to oral vitamin C formulations.

It is apparent that the full range of responses in the human population was not represented by the NIH study, as the current data are well outside their published maxima for depleted subjects. These values also exceed statistical expectations [17], derived from 15 000 subjects measured at Biolab in London. The estimated probability is too small (p51.6610213) to be considered accurate but provides a quantitative indication of the observed discrepancy. Additional research, to include populations not represented in the published data on depleted subjects, is clearly needed.

討論

這是第一份公佈的關於脂質體製劑維生素C對吸收影響的報告。這項初步研究涉及兩個項目,即針對美國國立衛生研究院所公布,一般人實施維生素C食療,研究後所發布的規範,他們兩個項目研究的結果都有問題,第一,他們所採樣人數在多樣性方面,採樣不足,僅達到需要採樣的樣品空間的10%而已,竟然就發布人類的服用標準。其次因受測樣板是局限於患有貧血患者的範圍,無法真正代表人的實際狀況,這與我們對正常人實施的口服脂質維他命C的實驗結果,產生很大差異。很明顯的,NIH研究是不能代表對一般人類真正的反應。因為目前我們所獲得的數據遠遠超出他們公布的最大值。他們的數據,也偏離了倫敦Biolab所獲得的對15 000名受試者的統計資料[17]。原因是他們預估值的樣板空間不足,造成很大的差異,其機率僅是(p51.6610213)的狀況,政府部門竟然就公布這有疑慮的資訊為標準數值。顯然我們真正需要做的是針對這僅僅對少數人不吻合大數的實驗,實施進一步的研究。

At over 100 um/L, the subjects’ baseline vitamin C levels, following a 12-hour washout period, were higher than those reported in the NIH studies used for the RDA [4,5].

以超過100um / L為準,受試者的維生素C濃度在12小時沖洗期後高於NIH研究報告,RDA所採用的資料,。 [4,5]

A possible explanation is that high vitamin C levels redistribute from the blood plasma into other body compartments and vice versa. Thus, subjects who habitually consume large amounts of vitamin C might carry a reserve in their tissues. Plasma vitamin C, which is depleted through kidney excretion, has a half-life of only 30 minutes.

可能的解釋是高維生素C濃度,是從血漿重新散佈到其他身體區域,反之亦然。因此,習慣性攝取大量維生素C的受試者可能在其組織中攜帶著儲備物。通過腎臟排泄而消耗的血漿維生素C的半衰期只有30分鐘。

However, while it is being excreted, it can be replaced by absorption from the gut or by redistribution from other body compartments.

然而,當維生素C被排泄後,可能會被來自腸道吸收的或通過從其他身體器官的再分配來代替。

The elevated baselines observed in these subjects are nconsistent with the NIH’s pharmacokinetic modelling of the plasma response of gram level doses of vitamin C [3–5].

在這些受試者中,所觀察到的數值升高的情形與NIH對克劑量維生素C的血漿反應的藥代動力學的模擬,並不一致[3-5]

Regular use of high dose vitamin C, given at intervals of 12 hours or less, produces baseline plasma levels greater than those the NIH study described as ‘saturated’.

定期的以12小時或更短的時間間隔攝取高劑量維生素C,產生的基準的血漿濃度,是遠大於NIH研究所得的“飽和狀態”的血漿濃度。

Since ‘saturation’implies a maximum level, which has been refuted by the higher levels reported here, use of this term (as employed by the NIH in the context of vitamin C plasma levels) should be considered obsolete, inappropriate and inaccurate and the word returned to its conventional meaning.

由於“飽和"兩字,是代表最高濃度,這已經被我們實驗的資料,獲得更高濃度之事實所推翻,因此使用這個術語(如NIH在維生素C血漿濃度文章所使用)應該被認為是過時的,不適當的和不準確的。

The plasma levels reported here are higher than is usually seen with oral administration of vitamin C, although the doses were also higher.

這裡報道的高劑量口服維生素C產生血漿濃度是高於通常所見。

Biolab noted that the plasma levels attained with 20 g and 36 g doses of liposomal vitamin C were higher than any they had measured previously, following oral doses. Biolab’s previous experience and measurement of plasma vitamin C levels has been consistent with the reference interval for human plasma

(34–114 um/L).

Biolab指出,口服20 g36 g劑量的脂質體維生素C,達到的血漿濃度高於之前測量的任何血漿濃度。Biolab以前的經驗和血漿維生素C濃度的測量與人體血漿的參考範圍是一致的(34-114um / L)。

Neonates and supplemented subjects with impaired renal function routinely record plasma ascorbate concentrations of up to 200 um/L.

新生兒和腎功能受損的受試者,正常記錄到的血漿抗壞血酸濃度高達200um / L

Since plasma levels in this study were outside the normally reported range, they were communicated to Dr Ron Hunninghake, Clinical Director of the International Center for the Improvement of Human Functioning, who carried out an independent replication.

由於本研究的血漿濃度已超出正常報導的範圍,因此這資訊傳到了國際人類功能改善中心臨床總監Ron Hunninghake博士,他們進行了一次獨立的再次複製的實驗。

Hunninghake, who acted as his own experimental subject, is a habitual high-dose vitamin C supplement user (10 grams per day). Using repeated doses of liposomal and standard vitamin C, at lower intakes than our 36 g maximum, Hunninghake determined vitamin C

levels in excess of 300 um/L.

Hunninghake他自己就是長期性的高劑量維生素C使用者(每天10克),他再次實施的實驗科目也是重複使用劑量相同的脂質體和標準維生素C,在攝入量低於我們最大值36克時,Hunninghake測定維生素C濃度也是超過300um / L

This level was achieved with 10 g of standard C, followed by an additional 12 or 18 g of liposomal C, divided at intervals through the day. Through this procedure, high vitamin C plasma levels were sustained, rather than peaking as in our single dose study.

這濃度是使用10g標準的維生素C,接著攝取1218g脂質體C,一天內分成多段時間間隔攝取,就能達到該濃度。通過這個程序,高維生素C血漿濃度能持續保持,而不是像我們的單劑量研究中得到的短暫峰值。

Following a washout period (no vitamin C intake), Hunninghake found he retained between 100–150 um/L, which supports our findings.

經過清洗期(沒有維生素C攝入)後,Hunninghake發現他能持續保持濃度在100-150um / L之間,這完全支持我們的發現。

Hunninghake’s laboratory (Bio-Center, Wichita) has  averaged ,2000 plasma C determinations each year since 1994; in 2006, they performed 6634 plasma measurements.

Hunninghake的實驗室(威奇塔生物中心)自1994年以來每年平均進行2000次血漿C的測定; 2006年,他們就進行了6634次血漿的測量。

Their background results (from 37–120 um/L) provide a reference range that is consistent with Biolab’s (34–114 um/L). The maximum value recorded at the Bio-Centre (from a cancer patient, taking ,100 g per day orally) was 318 um/L [18].

他們的研究結果(從37-120um / L)提供了與Biolab34-114um / L)一致的數據。這生物中心記錄到的最大值(來自癌症患者,每天口服100克)為318um / L [18]

The results of the present study, together with Hunninghake’s replication, clearly refute the NIH group’s suggestion that the blood is saturated with vitamin C at ,70 um/L.

本研究結果連同Hunninghake的複製實驗,顯然推翻了NIH公布的資料,亦即血液中飽和的維生素C70um / L

The similarity in the plasma response curves for liposomal vitamin C and the standard commercial formulation, shown in Figure 1 (5 g doses), is interesting. There is a hint that the liposomal form has a slower onset to peak level and a broader profile. Liposomes are absorbed from the gut and into the liver, before being released into the blood stream.

脂質體維生素C和標準商業製劑維生素C的血漿反應曲線的相似性如圖1所示(5g劑量)是非常有趣的。暗示著,脂質體維生素C的起始速度較慢,達到峰值濃度後就保持平穩狀態。脂質體是從腸道中吸收並進入肝臟,然後才釋放到血液中。

This response can be seen more clearly in the 20 g dose, in Figure 2. It is apparent that sustained levels of plasma ascorbate, above the previously assumed maximum of 220 um/L, are possible with oral intakes of liposomal vitamin C.

這種反應可以在20 g劑量實驗中更清楚地看出來,如圖2所示。顯然,口服維生素C能持續高於先前假定的最大值為220um / L的血漿抗壞血酸濃度是可能的。

Cathcart [19] describes a mechanism of increased bowel tolerance to oral ascorbate. He reports a direct correlation between the severity of illness and the maximum amount of ascorbate absorbed by the oral route.

Cathcart [19]說明了口服抗壞血酸鹽增加腸耐受性的機制。他的報告顯示疾病嚴重的程度,與口服途徑吸收最大量的抗壞血酸之間,有直接相關性。

These clinical observations indicate that the physiological response to ascorbate is variable; clarification awaits suitable pharmacokinetic studies in diseased patients.

這些臨床觀察證明,抗壞血酸的生理反應是可變化的;這方面需要等待對病患者,進行適當的藥代動力學的研究來澄清。

The results of this preliminary study are consistent with the suggestion that continuous vitamin C supplementation facilitates increased absorption of large doses.

這項初步研究的結果,證實連續攝取維生素C,有助於增大劑量吸收的看法是符合的。

The reference interval for vitaminC quoted for human plasma is 34–114 um/L [17]. In these experiments, the measured baseline levels for vitamin C were in the range 132–149 um/L.

維生素C進入人血漿的參考範圍值是34-114um / L [17]。但在我們這些實驗中,維生素C的測量濃度,可達到132-149um / L範圍內

This concentration is approximately twice the level found in previously depleted subjects. The mechanisms of absorption of ascorbate from the gut are not well understood.

這個濃度大約是以前受試者的兩倍。從腸道吸收抗壞血酸的機制尚不清楚。

Our experience suggests that subjects who habitually consume high intakes of oral vitamin C and subjects that are ill may show a differing response to those who were previously depleted.

我們的經驗證明,長期口服維生素C量高的人或是生病的病人。可能有不同的反應。

Physiological adaptation to ascorbate intake may involve recruitment of glucose transporters (GLUT4) signalled by insulin, cellular contraction or reactive oxygen species [20,21].

Our observations suggest that poor oral absorption is related to carbohydrate intake.

對抗壞血酸攝取的生理適應性可能涉及由胰島素,細胞收縮或活性氧的葡萄糖轉運蛋白(GLUT4)有關[20,21]

我們的觀察結果也證實,口服吸收不良的情形,會與碳水化合物攝入量有關。

Glucose and other sugars compete with dehydroascorbate for absorption by GLUT transporters.

葡萄糖會和其他糖與脫氫抗壞血酸發生競爭,並由GLUT轉換吸收。

The subjects in this study reported that they often consumed 10-grams or more of ascorbate in a single dose, without significant bowel effects, provided their carbohydrate intake was low. In the present study, the subjects reported no bowel effects or a slight constipation following the 5-gram doses.

本研究中的對受試者報告已指出,如果碳水化合物的攝入量較低,他們能常在單次劑量下,消化10克或更多的抗壞血酸,而沒有顯著的腸道不良反應。在本研究也顯示,5克劑量並無腸道不良反應或出現輕微便秘

The 20-gram liposomal dose was tolerated well. In these fasting individuals, the bowel reaction to the 36-gram dose may have been caused by the large intake of phospholipids, without food buffering.

人體對20克脂質體劑量耐受良好。在這些空腹受試人體中,對36克劑量發生的腸道反應,可能是由於大量攝入磷脂,而沒有食物緩衝所引起的。

The pharmacokinetics that form a principal evidence base for determination of the RDA values for vitamin C rely on results from a small number of depleted or previously depleted individuals. Such individuals may not be representative of all members of the population.

之前他們確定維生素CRDA值的主要依據,是藥代動力學仰賴於少量或以前舊的個案所建立的數據。這些個案,不能代表人類真實的狀況。

Well-nourished individuals, with Western levels of carbohydrate intake, who have been previously depleted of ascorbate, may have a low plasma response to oral ascorbate.

營養充足的人,或是習慣以西方飲食攝取大量碳水化合物的人,口服抗壞血酸後,可能會產生抵消抗壞血酸鹽的反應,導致血漿反應較低

In the present study, the levels attained from a single oral dose of five standard 1-gram tablets produced plasma levels above the predicted 220 um/L maximum level. Larger or repeated doses would have increased this level further.

在本研究中,單次口服劑量的5個標準1克片劑,產生的濃度,已高於預測的220um / L最大的血漿濃度。若給予更大或重複攝取劑量,會進一步提高這一濃度。

The ‘saturated’ baseline level, determined as 70–80 um/L in the NIH pharmacokinetic studies, is not an upper limit.

NIH藥代動力學研究中,“飽和”濃度所建立的70-80um / L數據,根本不是上限。

Baseline levels between 12–24 hours after a single oral dose are consistent with ascorbate transfer between blood plasma and other body compartments.

單次口服劑量後12-24小時的基準濃度,血漿和其他身體器官之間的抗壞血酸轉移是一致的。

In our study, the recorded background level after a 12-hour washout was in the range 132–149 um/L, approximately double that found in depleted individuals.

在我們的研究中,12小時沖洗後,記錄到的濃度是132-149um / L範圍內,大約是已排泄光的人體中,發現的兩倍。

This is consistent with increased tissue levels or sustained absorption from the intestine. We suggest the NIH’s assumption that plasma levels are tightly controlled and ‘saturated’ at 70–80 um/L was premature and thus the RDA for ascorbate could require revision.

這與增加在器官組織濃度或來自腸道的持續吸收是一致的。我們建議NIH所假定血漿濃度是受到嚴格控制下,建立的70-80um / L的“飽和”數據,是過早論斷的,因此抗壞血酸的RDA必需要修訂。

Our findings have important implications for therapy. The role of pharmacological levels of nutrients in cancer and other diseases is currently being re-evaluated [22].

我們的研究結果對疾病治療上有重要意義。目前正在重新評估這屬於營養物質的濃度,使用在癌症和其他疾病中的藥理學的作用[22]

In particular,the cytotoxic action of ascorbate on cancer cells suggests the possibility of a potentially non-toxic cancer therapy [23,24].

特別地,抗壞血酸對癌細胞的毒性作用,以及其潛在的無毒性方式對癌症治療。[23,24]

However, it has been assumed that cytotoxic levels of ascorbate could only be achieved with intravenous infusions of sodium ascorbate [8].

然而,目前僅認為,只能通過靜脈注射抗壞血酸鈉來實現[8]

This would be an implication of the available data, if oral doses could achieve only 220 um/L in plasma. However, we have demonstrated that single doses of liposomal formulations can

give levels above 400 um/L.

僅是已知的,口服就能在血漿中達到220um / L。 然而,我們已經證明僅一次服食脂質體製劑,就可以達到400 um / L以上的濃度。

If given in a single dose to a fasting individual, such intakes might be impractical. However, these preliminary findings suggest that plasma levels of 500–600 um/L or more could be sustained indefinitely with smaller, but repeated, oral intakes.

如果單次就給空腹的人體攝取,這種攝入可能是不切實際的。然而,這些初步研究結果表明500-600um / L或更高的血漿濃度,可以無限期地保持與存在人體血液之中,但要給予較小量但重複口服攝入。

Data for the cytotoxicity of ascorbate comes from laboratory experiments, performed over a timescale measured in hours.

抗壞血酸對癌細胞毒性數據來自實驗室實驗,都在數小時內進行測量。

However, tumours can selectively concentrate ascorbate from plasma. Published results for a 1-hour in vitro treatment of human Burkitt’s lymphoma cells, using ascorbate at 300 um/L, show ,30% necrosis and apoptosis; 400 um/L increases the cell death to ,50% [25].

然而,腫瘤可以從選擇性地使用濃度高的抗壞血酸消滅。當使用300um / L抗壞血酸時,對人類伯基特氏淋巴瘤細胞實施1小時體外治療的結果顯示,發生30%的壞死和凋亡; 使用400um / L濃度,可將細胞死亡增加到50[25]

Moreover, ascorbate cytotoxicity is synergistic with other oral nutrients, including alpha-lipoic acid [26], vitamin K3 [27] and copper [28].

此外,抗壞血酸鹽與其他口服營養素(包括α-硫辛酸[26],維生素K3 [27]和銅[28])產生協同作用,共同發揮消滅癌細胞的毒性。

The implications of sustained high concentrations of ascorbate may thus be therapeutically significant.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

因此,持續高濃度的抗壞血酸鹽的作用,可能是最顯著的抗癌治療方法。

聲明:作者這份報告,沒有任何利益上的考量。 作者完全對全部本論文的內容負責。

*****************************************

老船長親自翻譯,沒有版權,讓一切得到醫治的榮耀,都歸於我的主耶穌基督  阿門

脂質維他命 C 製作方法與抗癌服用:

1. 先預備30克的維他命C + 250 CC清水(把兩者搖勻)。

2. 預備90 克非轉基因卵磷脂 + 500 CC溫水(先浸泡3小時,再用果汁機高速將兩者混合約3秒)。

3. 把1 和2 放進果汁機高速60秒。

4. 將混合好的液體,用超聲波清洗機,處理8分鐘。完成脂質性維他命C製作。

5. 服食30g(含有1g維他命C)等於靜脈注射維他命C6克的份量。

6.一次攝取600克、或1080克的量(攝取20克、或36克維他命C)的脂質體維生素C,人體峰值血漿濃度,可到達300um / L 或是400um / L的區域,能維持數小時。當人體峰值血漿濃度達到300um / L時,對人類伯基特氏淋巴瘤細胞,實施1小時體外治療的結果顯示,發生30%的壞死和凋亡; 使用400um / L濃度,可將癌細胞死亡增加到50%。在對身體完全無礙條件下,能迅速消滅癌細胞。

7.這些初步研究結果表明500-600um / L或更高的血漿濃度,可以無限期地保持與存在人體血液之中,但要給予較小量但重複口服攝入。

警告:

因為攝取高劑量脂質維他命C,會對癌腫瘤產生強力的壞死和凋亡,問題是食療成功後這些腫瘤壞死的殘餘體,會繼續附著在人體器官上,還是脫落??

假設病人是腦瘤或是肺癌四期,雞蛋大小的腫瘤,壞死後若存留在原器官,腐敗後產生毒素,身體能自然排除嗎?還是需要手術取出???

詹姆士的成功擊敗四期口腔腫瘤,他是在45日的周期中,以穩定的注射高C讓癌細胞穩定的凋亡,而且目視就能看到過程(照片為證),算是完美的。這是屬於身體自然排除。

因此,要注意這個問題,操之過急,想幾天內就把癌細胞搞死,必有嚴重的未預料的後果發生。劑量必須循序漸進,我們還是需要醫師的協助。

哪裡購買?

1.左旋維他命C粉末 食品級

http://goods.ruten.com.tw/item/show?21444586623184

2. 超音波清洗機 2L數位型

https://tw.bid.yahoo.com/item/%E3%80%90%E6%AD%A3%E5%93%81%E5%85%AC%E5%8F%B8%E8%B2%A8%E9%99%84%E7%99%BC%E7%A5%A8%E3%80%91%E8%B6%85%E9%9F%B3%E6%B3%A2%E6%B8%85%E6%B4%97%E6%A9%9F-2L%E6%95%B8%E4%BD%8D%E5%9E%8B-%E9%99%84%E8%B4%88%E5%A1%91%E8%86%A0-100102881243

3.卵磷脂

http://goods.ruten.com.tw/item/show?11080911849293

100 mg/L  =  

 430 µmol/L

 

 

 

References

以下是參考資料(省略)

1. Dietary reference values for food energy and nutrients for the United Kingdom. Report of the Panel on Dietary

Reference Values, Committee on Medical Aspects of Food and Nutrition Policy. London: HMSO; 1991.

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