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The redoxsysteme Vitamin C has fascinated the author for more than eighty years. His first lecture, concerning this vitamin in general, was given in Dec 1945 in Thuringia, Germany, working there in addition to his research activities in Jena together with his father as head of pharmaceutical preparations and first rate spirit (Primasprit) at the Mühhausen branch of Leipzig company Dr.WILLMAR SCHWABE (Part V-A, p 359/60).
In this lecture,
the author defined Vitamin C as a vitamin complex consisting of L-ascorbic
acid / L-dehydroascorbic acid: Formulae IIa and IIb in Plate 1 as written
by Emil Fischer. The lactone rings (IIa/IIb) were opened by hydrolysis in the 2,3-diketogulonic
acid (IIc) formulated in this Plate, resulting in the elimination of the
biological equivalence of IIc (Part II, p. 710). In Plate 2 you see
ascorbic acid (I) and dehydroascorbic acid (II) including intermediates as
reversible redox system (and hydrates) in modern writing, in Plate 3 you see:
Stereomeric forms of ascorbic acid (I) with explanations below the plate.
Plate 1:
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| Plates 2 and 3 are taken from Part II, pp 724 and 726 | Definition: D,L in Part II, p 83 |
Later the Vit C was also regarded in the authors biochemical classes elaborated in 1947/49 at the Humboldt-University Berlin(EAST) and 1952/53 at the Free University Berlin(WEST), par example: Detection of Vit C in cow milk, mother milk etc. An Arabian student brought camel milk for quantitative Vit C determinations: We found unexpectedly that the Vit C content of camel milk is - compared with cow milk - twice as much. To further own investigations with Vit C led discussions with Linus Pauling whom the author met from 1957 on in California, USA, and later several times (important 1969, 1972) : Pauling had organized
- in the frame of his activities for the ortho-molecular-medicine of Walker -
in cooperation with Dr. Iwan Cameron - cancer prevention experiments in an English county: Vit C was given daily orally in inconsiderable amounts, challenged by physicians. The author asked Pauling whether tests had been carried out "how tumors react to Vit C applied intravenously", because the advantages vis-a-vis high oral daily administration are obvious, because when orally taken, only small amounts of Vit C will get into the blood. The author had not only cancer prevention in mind but also cancer therapy. Pauling's answer: "Not as far as I know. Also Dr. Iwan Cameron applied Vit C only orally (pure powder teaspoon-wise) in his cancer prevention experiments. – Keep me informed about your planned activities concerning Vit C injections in lab animals and patients in clinics in Berlin FU and in Santa Maria, RS, Brazil, UFSM, where you see the possibilities to realize your plans".
From 1970 on cooperation with Dr.med.Lipp[i], Robert-Koch-Institute, Berlin-Dahlem, the author was able to carry out experiments with ascites mice and rats, Vit C solutions injected into the tail vein of these animals: The positive results (Part I, p 191/2) of these animal experiments led to clinical activities together with Prof.Dr.med. H.Gerhartz[ii], Klinikum Westend, Dept.Oncology, Berlin(WEST), and later with Prof Dr.Mariano da Rocha Filho, University teaching hospital of UFSM, Brazil, described in Part II, p 728-730. The author delivered - in the beginning of all these Vit C injection experiments - a solution with 100mg Vit C in 100 ml aqua injectabilis, buffered according to the desire of Prof.Gerhartz's; cf. Part I, p 192, in footnote 2 details. Today it goes without saying that Vit C injections found their way to cancer therapy.
L Pauling and the ortho-molecular-medicine, founded by the American nutrition specialist Norman W.Walker, the physician Max.Otto Bruker, and the biochemist Irwin Stone, taken over in 1966 by Pauling which led to the Institute of Science and Medicine founded later in Palo Alto, Ca., USA).
Definition of “ortho-molecular medicine” according to R.Rowghani[iii]:
“L. Pauling geht bei der menschlichen Gesundheit davon aus, dass man in den gesamten Körperzellen „gut angeordnete Moleküle“ vorfindet, ein zu erreichender Zustand, welchen Pauling in den 60er Jahren ORTHOMOLEKULAR nennt (orthos = richtig; molekular = Moleküle betreffend). So entstand die mittlerweile bekannt gewordene und bei Ärzten angewandte ORTHOMOLEKULARE HEILKUNDE, die besagt, dass der Mensch erkrankt, wenn er nicht mehr in den Körperzellen die lebensnotwendigen Moleküle aufweist, was zuerst zu Fehlfunktionen und schliesslich zu bisweilen schweren Krankheiten führt.“
According to the author’s opinion . Norman W. Walker had achieved pioneer work in this field; and as result of living in this way:
- Walker himself reached an age of 116 years.
- Pauling reached an age of 93 years.
Walker founded the “Norwalk Laboratory for Nutrition and Research” in New York in 1910.
Proper nutrition and sufficient physical exercise belong to a healthy life. Every physician should discuss these rules with his new patients before writing any prescription - so avoiding unnecessary application of remedies[iv].
Without Pauling’s activities in ortho-molecular medicine and without Pauling’s much criticised "extensive oral Vit C experiments for cancer prevention in an English County“ the author would not have continued with the development "synthetic organ extracts" leading in Japan to CELLRYL[v] and would not have initiated the mentioned Vit C injection experiments with lab animals and not have dared to organize "clinical Vit C interveneously cancer prevention and therapy expts" in Berlin: Klinikum Westend, FU (Prof.H.Gerhartz), and in Brazil, UFSM, University hospital (Prof.J.Mariano da Rocha Filho), starting in the 1970ies.
Another important side of Vit C is his "role" as stabilizer:
The vitamin C complex (formulated in Plate 1) itself is stable if one of the three factors H2O, O2 and metal ions can be excluded. In the presence of O2 the component IIb is dominant in aqueous vitamin C solutions, evident from his yellow colouring. In order to remove oxygen from filled vessels to be sealed, the amount of vit C calculated for oxygen (+10%) was added. More details and practical applications in Part II, p 709/10, refs.there: (10a-h, 11) on p 733/15
Vitamin-based antioxidants like I: tocopherols (vitamin E) + vitamin C [ascorbic acid, ascorbates, ascorbyl palmitate II)]
I has the purpose of protecting food against decay, against auto-oxidation of its fats by O2. The risk for fats is the greater the higher their content of unsaturated fatty acids is; triggering or accelerating factors of this auto-oxidation are light, heat, the water content, heavy metals, pigments (porphyrin dyes), the surface. These factors cause the formation of free radicals which triggers a radical chain reaction. Vitamin-based radical scavengers are the ones cited above. The following synergists enhance the activity of phenolic anti-oxidants by complexing heavy metals: citric acid (III), succinic acid, tartaric acid, phosphoric acid.- II is 6-palmitoyl-L-ascorbic acid, a faintly yellow powder.
In practice, a combination preparation of II, alpha-tocopherol und III is used as an anti-oxidant. Its use: early, most preferably during the production of the fatty product.
Vit C as an important component in cosmetic additives to protect the skin
1964, as visiting professor at Kyoto University the author reported there about his "Vit cancer provision and cancer therapy experiments (Vit C intravenous)". Prof. Dr. S.Takei and Dr.M. Nakajima organized the authors cooperation with Dr.med Nagara and assistants to study "skin protection by Vit C in detail": Exact skin observation of lab animals, then of patients during the Vit C application with new physical methods (i.e.diff. light) over months (daily control) in the frame of the gerontological research of M.Nagara, M.Nakajima, author[vi], records of 1965-1972[vii]), filling 5 Leitz files: positive results unpublished, but used over years in all our cosmetic additives (delivered to Japanese customers) like OMNITHYMUS, CYTOCATALYZERs etc, bottling under N2 (except a reaction with O2 is wanted or permitted).
Plate 4: Methadon and some analogues (methadon = Nr.1)
R1
H3C-CH2-CO-C-CH2-CH-CH3
R2 N(CH3)2
R1 R2
1 C6H5 C6H5
2 C6H5 CH3
3 C6H5 C2H5
4 C6H5 CH2C6H5
5 CH3 CH3
Because methadon (1) in the Acites-mice test of prevention-cancer-expts increased the Vit C effect, also some I-analogues (Plate 4) in combination with Vit C were tested; The combination of Vit C + methadone (Nr.1) was the best regarding the Ascites reduction.
The experimental data of these expts and the preparation of compounds 2-5, their IR-spektra and data of test expts will be published later.
Summary
Vit C, important for and in the human organism: as redoxsystem ascorbic acid/ dehydroascorbic acid, as radical scavenger, oral and intravenously since 1970 applied in cancer prevention and cancer therapy, used as active component in cosmetic additives for skin protection (also as Na-ascorbat), as stabilizer, as antioxidants (in combination with Vit E and citric acid); the role of Vit C in ortho-molecular medicine according to Linus Pauling and the meaning of Pauling in the life of the author: see ADDENDUM to this essay: Proper nutrition important to cover the daily Vit C consumption [in addition: daily sufficient exercise belongs to a healthy life (sport)].
Betrifft: O r i g i n a l p r o t o k o l l e der
Intravenöse Injektionen von Vit C-Lösungen an Ascites-Mäuse und Ascites-Ratten durch Verfassers Habilitanten Dr.Lipp, tätig im Robert-Koch-Institut Prof.Hennebergs, sowie nachfolgender klinischer Versuche:
a) durch Prof.Dr.H.Gehartz, Berlin, Westend-Klinik, und
b) durch Prof.Dr.Jose Mariano da Rocha Filho, Uni-Hospital, UFSM, Brasilien
Beobachtung der Haut während der Vit C-Applikation mit neuen Methoden
Nach positivem Verlauf mehrjähriger, gemäß Titel angestellter Versuche mit Laboratoriumstieren, sind nach Angaben des Verfassers entsprechende klinische Untersuchungen gemäß a) und gemäß b) durchgeführt worden:
Die Herstellung aller eingesetzter Vit C-Lösungen ist genau protokolliert worden, d.h. es wurde ihr Gehalt an Ascorbinsäure / Dehydroascorbinsäure[viii] bestimmt, und zwar nach Justierung des pH-Wertes, angepaßt ans pH des Blutes der Versuchstiere bezw. der Versuchspersonen. Ebenso auch protokolliert worden ist jeweils die Menge der intravenös injizierten Vit C-Lösungen[ix] sowie der Zeitpunkt jeder Verabreichung, bei Patienten Notiz des Verhaltens der Krebssart sowie Blutdruckmessung(en), gegebenenfalls auch Abnahme und sofortige Untersuchung von Blutproben während der Behandlung.
Alle Originalprotokolle waren unter der Obhut von Dipl.-Chem.H.J.Hein – wie auch viele andere wertvolle Dokumente und Substanzproben – aufbewahrt worden im Biochemie-Institutsgebäude Limonenstraße: Leider vernichtet laut Hein's Dokumentation durch die studentische Arbeitsgruppe, die gegen den Willen des Verfassers dort einquartiert worden war; siehe Dokumentation Hein in Part V-B, p 953/4
ADDENDUM:
The above-mentioned meetings with Linus Pauling did not only have vitamin C as a topic. The discussions with this remarkable man in 1957 and 1964 had a decisive influence on the author's life:
1957: The author was debating whether he should stay in the United States or accept the call to the Chair of Biochemistry at the Free University of Berlin. Pauling said: "USA is nothing for you, accept your first call in Germany: Chair of Biochemistry at the FU Berlin".
1964: Pauling’s advice concerning the call of the UFSM, Brazil: "Remain in Germany, but organize simultaneously the wanted Chemical Central Institute of the UFSM as you need it and like it between 1964 and the 1970es in Brazil, staying about two months a year in Brazil for this time. See the immense possibilities for your research in future. The Brazilian Government pays all. Prof Richard Kuhn, Prof.h.c. at UFSM, shares my opinion: Kuhn knows well your papers concerning cis-trans-asymmetry and axis-ring-compds and studied you when you had given a lecture in Heidelberg on May 15th, 1955 [(466a) in Part II, p 770] Authors thoughts writing this: Did Pauling and Kuhn perhaps have a kind of presentiment of the coming disaster in form of BerlHG 1969 (so-called democratization of the FU)? See also the essay "Past Politicalization" in Part V-B, p 337-350.
i belonging to the "Biochemical Basic Class", Part V-A, p 129. - See Part V-A,p 519: some refs. to Vit C, C-injection expts. on p 520