Cell Membranes Part 2: Restoring Cell Membrane Function
Dan Carter, ND
Introduction
In part 2 we will examine approaches to improve the state of membrane function, seeing
that the cell membrane can indeed by resuscitated, improving cellular function and
patient health. In order to accomplish this, we need to supply membrane substrates in
their most beneficial form and via appropriate routes of administration.
Phospholipids
Increasing the amount of beneficial phospholipids is accomplished through oral
supplementation or intravenous (IV) administration. To maximize membrane fluidity the
most beneficial phospholipid is 1,2 dilinoleoylphosphatidylcholine, also called Polyenyl
PC (PPC). The fatty acid tails of PPC are both linoleic acid, an omega-6 doubly
unsaturated fatty acid; PPC is derived from soy. In contrast, the phospholipid (lecithin)
derived from egg is distearoylphosphatidylcholine, with both fatty acid tails being
saturated palmitic acid. Liver disease will be used as an example of PPC benefits.
Treatment with two grams phosphatidylcholine (PC) daily for two weeks resulted in 50%
decrease in ammonia levels in patients with cirrhosis and hepatic encephalopathy. 1
Marked improvement of liver function following phosphatidylcholine administration in
terms of an increase in metabolic and detoxifying capacity of liver was noted.2 Although
the following study was not restricted to cirrhosis, 650 subjects with varying liver
damage were followed for five years. Patients received 950 mg IV PC and 450-700 mg
oral PC, when labs normalized they received oral PC only. All groups benefited and
showed reversal of fatty degeneration and recovery from acute inflammation
accelerated.3 Research has shown that phosphatidylcholine has striking hepatoprotective effects. Two animal studies using baboons fed diets high in alcohol, one
group supplemented with a soy-derived polyunsaturated lecithin (60%
phosphatidylcholine) and the other group unsupplemented, both fibrosis and cirrhosis
were mostly prevented in the phosphatidylcholine group. Most of the unsupplemented
animals in the studies, which continued for eight years, developed fibrosis or cirrhosis.4
In addition, phosphatidylcholine has demonstrated other protective effects in nonalcoholic liver disorders, including protection against various other toxic substances. Its
benefits in viral hepatitis were reported some years ago by several different research
groups in Europe and elsewhere. In one of these studies, individuals suffering from
hepatitis type A and B were given 1.8 grams of phosphatidylcholine daily. Compared
with unsupplemented controls, the phosphatidylcholine group enjoyed quicker
recoveries, fewer relapses and quicker normalization of liver function tests.5, 6, 7, 8
Cell Membranes Part 2: Restoring Cell Membrane Function
Dan Carter, ND
PC is also useful for hepatitis C. In a multicenter, double-blind trial, 176 patients with
chronic viral hepatitis, either B or C, were started on interferon alpha for 24 weeks and
were then randomized to PC (1.8 g/day) or placebo for 24 weeks. Significantly more
patients responded to PC, predominantly in the hepatitis C subgroup. Additionally, PC
supplementation sustained a longer-term improvement from hepatitis C over another 24
weeks.9
Fatty acids
Numerous reports have established that lipid peroxidation causes cell injury by altering
the fundamental physical properties and structural organization of membrane
components.10 Dietary fatty acids can renew damaged membrane lipids by fatty acid
exchange.11, 12 The objective is to supply essential fats in a non-damaged form, in other
words alpha-linolenic acid (omega-3) and linoleic acid (omega-6) that are not oxidized
or in trans-configuration. Lipid oxidation can occur in food processing and
preparation,13 or as a naturally ongoing process in the body via the effect of reactive
oxygen species.14 The objective then becomes to avoid oxidized fats in foods and
replace the oxidized fats in cell membranes with non-oxidized fats. Avoiding damaged
dietary fats is easier than dealing with the internal process. Eating a whole food diet,
cooking meats at low temperature (Crock Pot, stewing), using stable fats such as olive
and coconut oil, elimination of grains if sensitive (wheat is most common), and avoiding
simple sugars really cuts down on the oxidative load. If a person is diabetic, then blood
sugar control is extremely important as high blood sugars are very pro-oxidative. The
essential fatty acids can be restored with specific supplements such as (organic cold
extraction process) hemp oil (3:1 omega-6:omega-3) or properly processed organic flax
meal or oil (1:4 omega-6:omega-3).
Protecting and correcting the internal environment is more challenging. “Enzymatic
(catalase, superoxide dismutasse) and nonenzymatic (vitamins A and E) natural
antioxidant defense mechanisms exist; however, these mechanisms may be overcome,
causing lipid peroxidation to take place. Since lipid peroxidation is a self-propagating
chain-reaction, the initial oxidation of only a few lipid molecules can result in significant
tissue damage.”[Ref 13] It would be wise to have patients taking a balanced water and
fat-soluble antioxidant supplement using non-synthetic nutrient sources.
When lipid peroxidation overcomes natural defenses it is more efficacious to go with a
fat-soluble antioxidant such as alpha lipoic acid (ALA) administered IV. Many viral
infections, including hepatitis C, induce increased oxidative stress on target tissues.15
Toxins may also result in oxidative stress that is life threatening due to depletion of liver
glutathione, e.g acetaminophen16 and amanita mushroom (Amanita phalloides).17
Acetaminophen toxicity is treated with N-acetyl-cysteine (NAC), whereas mushroom
Cell Membranes Part 2: Restoring Cell Membrane Function
Dan Carter, ND
toxicity has been treated with NAC and silibinin (water-soluble milk thistle extract), as
well as ALA.18 Another recent study used a combination of ALA and alpha-tocopherol to
treat acetaminophen generated oxidative stress.19
Toxic metals are known to cause oxidative damage to bio-molecules by initiating free
radical mediated chain reactions resulting in lipid peroxidation, protein oxidation and
oxidation of the nucleic acids DNA and RNA. ALA is a useful treatment consideration
due to its dual actions as an antioxidant and toxic metal chelator.20
Oxidized LDL (Low density lipoprotein) cholesterol
All of the lipoprotein particles associated with cholesterol transport through systemic
circulation are microscopic spherical micelles composed of a mono-layer of
phospholipid, associated protein, and in the case of LDL this is apoprotein B-100; the
core is composed of cholesterol esters and triglycerides. The American diet contains
large quantities of oxidized fatty acids and oxidized cholesterol because a large portion
of the fat and cholesterol in the diet is often prepared in a fried, heated, or processed
form.21
Linoleic acid (the omega-6 fatty acid found abundantly in industrial seed oils) is the main
polyunsaturated fatty acid in LDL, due to its common presence in processed foods. It
has been found that diets high in (damaged, oxidized) linoleic acid results in faster LDL
oxidation in comparison with and oleate (olive oil) diet.22 A 2008 study noted that dietary
consumption of olive oil improved the fatty acid profile in LDL, the changes being
associated with a reduction of the oxidative damage to lipids.23 Oxidized LDL damages
the endothelial cell monolayer and appears to play a pivotal role in initiating and
deteriorating thromboembolic complications.24
Antioxidant vitamins
Supplementation with vitamin C or vitamin E alone diminished lipid peroxidation to a
similar amount. Supplementation with a combination of vitamins C and E resulted in no
benefit beyond that of either vitamin alone.25 A 2001 study in JAMA revealed that
healthy individuals did not appear to benefit from supplementation with alpha-tocopherol
when lipid peroxidation was measured.26 More recent research supports
supplementation with a full spectrum vitamin E (mixed tocopherols) to attenuate
oxidative/inflammatory damage to endothelium.27
Summary
 Evaluate the patient and determine the principle pathology and order of
treatment.
Cell Membranes Part 2: Restoring Cell Membrane Function
Dan Carter, ND



Sicker patients require IV treatment. A toxic metal pre and post provocative
challenge test is appropriate (urine). If significant toxic metal loads are present,
IV chelation using Ca-EDTA or DMPS (as appropriate) should be administered.
Nutrient IVs should be administered 2 days post chelation at a ratio of 1:1 to 1:5
(nutrient/chelation), with more ill patients at a higher ratio.
A series of 30-60 IV treatments with polyenyl phosphatidylcholine (PPC). This not
only helps restore cell membranes, and thus cell functionality, but also decreases
atherosclerotic plaque load. Due to compounding issues surrounding the
manufacture of quality PPC the author recommends Plaquex (no financial conflict
of interest).
Patients with liver involvement, viral diseases, or mitochondrial collapse will
benefit from IV lipoic acid infusions.
IV Therapy Reminder: All of the above IV protocols need to be infused separately; the
drugs are not compatible with each other in IV bags. They can be infused sequentially;
IV lines should be flushed between treatments. Appropriate IV training using these
drugs is assumed.



Avoid food sources of oxidized fatty acids and oxidized LDL, as well as transfats. Low sugar diet and control of diabetic blood glucose levels are imperative.
High blood sugars are significantly oxidative.
Replace essential fatty acids with cold processed organic hemp or flax oil. Marine
omega-3 oils are helpful when the inflammatory pathways are over reactive.
Give a spectrum of naturally derived (non-synthetic) fat and water soluble
antioxidants.
References
1
Vnitr Lek 2000 Apr;46(4):199-204.
Pogromov, AP et al. Klin. Med. (Moscow)10(1978)97.
3
Med Monatsschrift 27:131-137, 1973.
4
Lieber CS, De Carl LM, Mak KM, et al. Attenuation of alcohol-induced hepatic fibrosis by
polyunsaturated lecithin. Hepatol. 1990; 12:1390-1398.
5
Atoba MA, Ayoola EA, Ogunseyinde O. Effects of essential phospholipid choline on the course of acute
hepatitis-B infection. Trop Gastroenterol. 1985; 6:96-9.
6
Jenkins PJ, Portmann BP, Eddleston AL, Williams R. Use of polyunsaturated phosphatidylcholine in
HBsAg negative chronic active hepatitis: results of prospective double-blind controlled trial. Liver. 1982;
2:7-81.
7
Kosina F, Budka K, Kolouch Z, et al. Essential cholinephospholipids in the treatment of virus hepatitis.
Cas Lek Cesk. 1981; 120:957-960.
8
Visco G. Polyunsaturated phosphatidylcholine in association with vitamin B complex in the treatment of
acute viral hepatitis B. results of a randomized double-blind clinical study. Clin Ter. 1985; 114:183-188.
2
Cell Membranes Part 2: Restoring Cell Membrane Function
Dan Carter, ND
9
Niederau C, Strohmeyer G, Heintges T, et al. Polyunsaturated phosphatidylcholine and interferon alpha
for treatment of chronic hepatitis B and C: a multicenter, double-blind, placebo-controlled trial.
Hepatogastroenterol 1998;45:797-804.
10
Jacob RF, Mason RP. Lipid peroxidation induces cholesterol domain formation in model membranes. J
Biol Chem. 2005 Nov 25;280(47):39380-7. PMID: 16195227.
11
Bibb C, Young RW. Renwal of fatty acids in the membranes of visual cell outer segments. J Cell Biol.
1974 May;61(2):327-43. PMID: 4827908
12
Kildonk E, et al. Effect of phospholipid fatty acid composition of endothelial cell on cholesterol efflux
rates. J Lipid Res. 1992 Sep;33(9):1373-82. PMID: 1402104
13
German JB. Food processing and lipid oxidation. Adv Exp Med Biol. 1999;459:23-50. PMID: 10335367
14
Mylonas C, Kouretas D. Lipid peroxidation and tissue damage. In Vivo. 1999 May-Jun;13(3):295-309.
PMID: 10459507
15
El-Kannishy G, et al. Persisten oxidative stress in patients with chronic active hepatitis C infection after
antiviral therapy failure. Saudi J Gastroenterol. 2012 Nov-Dec;18(6):375-9. PMID: 23150023
16
From the website: http://www.globalrph.com/toxicology.htm, accessed 11.18.2013.
17
Grabhorn E, et al. Successful outcome of severe Amanita phalloides poisoning in children. Pediatr
Transplant. 2013 Sep;17(6):550-5. PMID 23721499.
18
Becker CE, et al. Diagnosis and treatment of Amanita phalloides-type mushroom poisoning: use of
thioctic acid. West J Med. 1976 Aug;125(2):100-9. PMID: 788340.
19
Sudheesh NP, Ajith TA, Janardhanan KK. Hepatoprotective effects of DL-alpha-lipoic acid and alphatocopherol through amelioration of the mitochondrial oxidative stress in acetaminophen challenged rats.
Toxicol Mech Methods. 2013 Jun;23(5):368-76. PMID 23343353.
20
Flora SJ, Shrivastava R, Mittal M. Chemistry and pharmacological properties of some natural and
synthetic antioxidants for heavy metal toxicity. Curr Med Chem . 2013;20(36):4540-74. PMID: 24206124.
21
Staprans I, et al. Oxidized cholesterol in the diet is a source of oxidized lipoproteins in human serum. J.
Lipid Res.
2003 Apr;44(4):705-15. PMID: 12562864.
22
Abbey M., et al. Oxidation of low-density lipoproteins: intraindividual variability and the effect of dietary
linoleate supplementation. Am J Clin Nutr. Mar;57(3):391-8. PMID: 8438773.
23
Cicero AF, et al. Changes in LDL fatty acid composition as a response to olive oil treatment are
inversely related to lipid oxidative damage: the EUROLIVE study. J Am Coll Nutr. 2008 APR;27(2):31420. PMID: 18689564.
24
Liu B, et al. Oxidized LDL damages endothelial cell monolayer and promotes thrombocyte adhesion.
Am J Hematol. 1998 Apr;57(4):341-3. PMID: 9544981.
25
Huang HY, et al. Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results of a
randomized controlled trial. Am J Clin Nutr. 2002 Sep;76(3):549-55. PMID: 12197998.
26
Meagher, EA, et al. Effects of vitamin E on lipid peroxidation in healthy persons. JAMA 2001 Mar
7;285(9):1178-82. PMID: 11231747.
27
Mah E, et al. Supplementation of a γ-tocopherol-rich mixture of tocopherols in healthy men protects
against vascular endothelial dysfunction induced by postprandial hyperglycemia. J Nutr Biochem. 2013
Jan;24(1):196-203. PMID: 22841396.
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Dan Carter, ND, graduated from National College of Naturopathic Medicine (NCNM) and
completed a 2-year family practice residency. He was appointed to a full-time faculty position in
1997 and served as a core faculty member through 2003. He has been in private practice in
Bozeman, Montana since 2004 and is currently offering expert consulting services focusing on
cardiovascular disease, metabolic syndrome, hormone restoration and IV nutrient therapies.
Dan has been an ACAM member since 2007 and has been a speaker at past ACAM conferences.