DCA and LAMC - Anderson Protocol.pdf

Paul Anderson

A rational and safe combination therapy using DCA and support LAMC in advanced cancers. Based on a cell line study showing synergy a small human case series was initiated. Positive results in non responsive cancers was shown.

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Integrative Oncology

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Integrative Oncology

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Rationale for and Protocol for the use of combined Dichloroacetate (DCA) and Lipoic Acid Mineral Complex (LAMC) in advanced Cancer Patients as developed by Paul S. Anderson for patients treated at Anderson Medical Specialty Associates and in the Bastyr University Clinical Research Center (BCRC).

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Cell Line Study:

We completed the assays using DCA and Lipoic Acid Mineral Complex (LAMC). These cell death assays utilized the U-87 glioblastoma cell line. This SRB protocol is identical to the one used by the NCI in their chemotherapy screen. (1) Protocol: In this experiment we chose 3 dosages of LAMC (as the proprietary formulation Poly MVA) (1,000; 500 and 100 uM) and 3 dosages of DCA (100, 50 and 10 mM). The glioblastoma cells are allowed to adhere to the culture plates for 24 hours. This was followed by a 48 hour exposure to LAMC alone, DCA alone and LAMC + DCA. The cells were then stained for viable cells and absorbance read for quantification. Results: The equivalent 8 tsp/day treatment dose of LAMC is the 1,000 uM, so we additionally looked at half the treatment dose (4 tsp/day equivalent) and 1/10th the treatment dose (approximately 3/4tsp/day equivalent) of LAMC. Normally, there is no significant difference at the 100 uM LAMC dose, in these assay conditions (cells do die if you wait for a longer period of time), and approximately a 41% reduction at 500 uM of LAMC. In regard to the DCA, the literature states that cell death occurs between 50 and 100 mM. Our data demonstrated a statistically significant reduction only at 100 mM. Normal cell death (i.e. neuropathy in animals occurs at approximately 75-80 mM equivalent dose). There was no different between glioblastoma cells treated with DCA at 10 mM and the control wells.

© www.ConsultDrA.com - Paul S. Anderson 2016 (All rights reserved) 2 There appears to be a synergistic effect between LAMC and DCA. While neither 10mM of DCA nor 100uM LAMC resulted in a significant reduction in the number of glioblastoma cells alone, together they caused a statistically significant 17% reduction in cell survival. In addition, 10 mM of DCA increased the effectiveness of 500uM of LAMC from 41% cell death to 63% cell death. In addition, the 50 mM DCA alone, which resulted in an only 15% reduction in cell survival, jumped to a statistically significant 45% reduction when only 100uM of LAMC was added. Interestingly, 5x less DCA (50mM below versus 10nM above) was needed to get about a 15% reduction decrease in cell survival when only 100 uM of LAMC was added to the 10mM DCA.

00.050.10.150.20.25Control10 mM DCA100 uM Poly-MVA + 10 mMDCA500 uM Poly-MVA + 10 mMDCA1000 uM Poly-MVA + 10 mMDCA

C e l l S u r v i v a l ( A b s o r b a n c e )

U-87: DCA 10 mM + LAMC (Poly-MVA)

17%63%93%ND

Figure #2

00.050.10.150.20.25

Control500 uM Poly-MVA500 uM Poly-MVA + 10 mMDCA500 uM Poly-MVA + 50 mMDCA500 uM Poly-MVA + 100 mMDCA

C e l l S u r v i v a l ( A b s o r b a n c e )

U-87: LAMC (Poly MVA) 500 uM + DCA

41%63%93%92%

Figure #3

© www.ConsultDrA.com - Paul S. Anderson 2016 (All rights reserved) 3 In summary: The ability of LAMC and DCA to manipulate the metabolic cascade resulted is a synergistic effectiveness. This allowed less DCA to be utilized and still demonstrate maximum effectiveness. These in vitro data support the concept that LAMC and DCA could be used to together effectively, since they both potentiate the effectiveness of the other. -------------------------------------------------

This cell line data alongside the mechanistic probability of synergistic activity between the two agents (outlined below) led to the idea to combine them as a therapy in cancer non-responders. Why consider DCA with LAMC:

Theoretical overview for the potential synergy of LAMC and DCA - The cell line study recounted above as well as the potential for the two agents to have not only physiologic mutual benefit but a theoretical collaborative anti-tumor benefit. The proposed anti-tumor benefit is that the two agents may work in similar manners to effect tumor cell damage. The potential physiological benefit is that typical DCA use requires cell protective support during treatment. LAMC has been shown to be neuroprotective and helpful in supporting the mitochondrial complex. (2,3,4,5)

00.050.10.150.20.25

Control50 mM DCA100 uM Poly-MVA + 50 mMDCA500 uM Poly-MVA + 50 mMDCA1000 uM Poly-MVA + 50 mMDCA

C e l l S u r v i v a l ( A b s o r b a n c e )

U-87: DCA 50mM + LAMC (Poly MVA)

15%45%93%93%

Figure #4

DCA mechanism Information:

See the white paper

“DCA Summary” as prepared by PS Anderson for the Bastyr Clinical Research

Center. Available through www.consultdra.com

LAMC (Poly-MVA) Mechanism of Action Information: (1)

A redox molecule that facilitates energy charge transfer at the cellular level with regards to the cellular transport chain, it can therefore protect and provide energy. Mimics the electron transport chain. Differs from free radical scavengers (e.g. alpha-lipoic acid) since there is no free lipoic acid or palladium. They are irreversibly bound together resulting in a molecule that is both fat and water soluble. LAMC (Poly-MVA) is a polymer (liquid crystal) rather than a single molecule. Therefore, the polymer provides a unified redox (accept charge and donate charge) reaction. In summary it is an extremely effective energy transferring molecule. --------------------------------------------------

Protocol as developed at Anderson Medical Specialty Associates:

Current combination therapy in trial using both oral and IV DCA- LAMC regimens

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Patient Selection: Patients chosen due to lack of response or failure of other therapies Includes failure of standard treatment plus at least one alternative therapy

Dietary Intervention:

Patients are on a modified ketogenic or low carbohydrate diet Patients are taking Vitamin A orally at 25,000 IU Retinol (not a carotenoid) PO QD

Dosing: First IV:

LAMC (Poly-MVA) at 40 mL IV or PO (Adult dose) - (PO in divided doses or IV in one dose)

** START WITH A 10mL LAMC TEST DOSE AND RAMP UP to 40 mL AS TOLERATED

IV dose is mixed in 500 mL Normal Saline or D5W and administered over 60

–

75 minutes Always administer the LAMC IV first No other additives are mixed in the LAMC IV For dosing i

n children use Clark’s rule:

Appendix A

Second IV:

DCA dosed at levels recommended by Anderson and Kahn (6,7) IV: 50-80 mg/kg IV in 500 mL normal saline and administered over 90-120 minutes.

** ALWAYS START WITH A LOWER (25 mg/kg) TEST DOSE AND RAMP UP AS TOLERATED.

Increase the volume of saline in patients who react during the smaller faster IV protocol.

Intervention Schedule:

Dose schedule is four to five days weekly if tolerates at a rotation of four to five days on and three to two days off. If detoxification symptoms such as headache, itching, non-anaphylactic skin erythema or others occur a three day per week alternating schedule of three days on protocol and four days off protocol may be attempted. As an example a Monday - Wednesday

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Friday on protocol and the balance of the days off.

Monitoring for reactions to therapy:

Detoxification symptoms of DCA as typically mediated by glutathione S-transferase zeta (GSTz) are generally responsive to increased thiol support with IV glutathione, oral Alpha Lipoic Acid or N-Acetyl Cysteine, but are rarer in this combined therapy as the LAMC has Alpha Lipoic Acid as a constituent. Patient reactions can include fatigue, headache, temporary cognitive

effect (“brain fog”), lethargy, body

aches and other symptoms associated with glutathione detoxification effect.

If these occur consider lowering the dose of both agents, increasing the diluent of each IV to up to 500 mL per agent, spreading the IV treatments out over a longer period or all of the above. Clinical reassessment is critical in attenuating these events. Preliminary Outcomes:

Use of combination therapy in non-responders: (All failed multiple therapies including high dose IVC as well as other Natural - Integrative Rx) Early results in seven cases:

[+]

One lymphoma patient (NH Follicular lymphoma) 66 YO male on admission Stabilized and then regressed chest masses with oral protocol Significant increase in QOL Patient is alive at year 4.5 and was originally given 6 months to live.

[+]

One ALL-AML (MLL+) patient 4 YO female on admission (Dx at 11 weeks of age, disease re-activated at 4YO) First therapy which eliminated peripheral blasts (confirmed by return of blasts during withdrawal of DCA-Poly tx)

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IV protocol 5 days per week Used through DLI transplant and other trial chemo tx.

[-/+]

One GBM patient 52 YO female on admission Aggressive GBM s/p resection X2 and failed chemotherapy

© www.ConsultDrA.com - Paul S. Anderson 2016 (All rights reserved) 6 Early in therapy patient shows definite CNS effect with each treatment Patient had positive quality of life effect but GBM progressed

[+]

Two Multiple Myeloma patients (1)71 YO female on admission After three weeks kappa chain values decreased significantly IV one day and oral 4 days per week (changed to oral protocol after week three) (2) 53 YO female on admission Results are too early to call

[+]

One CLL Patient 72 YO Female (Positive pain reduction and energy / quality of life.)

[-]

One end stage Metastatic Melanoma patient Update as of 12-5-

13 “No apparent

help from tx”

---------------------------------------------------------- References:

1. Cell death assay (U-87 glioblastoma cell line) provided by: Frank Antonawich, Ph.D. Senior Scientist and Clinical Research Administrator Garnett McKeen Laboratory, Inc. 2. Menon, A., and Nair, C.K.K. (2011) Poly MVA

–

a dietary supplement containing alpha-Lipoic Acid Mineral Complex , enhances cellular DNA repait. Int. J. Low Radiation, in print. 3. Ramachandran, L., Krishnan, C.V., Nair, C.K.K. (2010)

Radioprotection by α

-Lipoic Acid Mineral Complex formulation, (POLY-MVA) in mice, Cancer Biotherapy and Radiopharmaceuticals, Vol. 25, No.4, 395-399. 4. Menon, A., Krishnan, C.V., Nair, C.K.K. (2009) Protection from gamma-radiation insult to antioxidant defense and cellular DNA by POLY-MVA, a dietary supplement containing palladium lipoic acid formulation. Int. J. Low Radiation, Vol. 6, No.3, 248-262. 5. Menon, A., Krishnan, C.V., Nair, C.K.K. (2008) Antioxidant and radioprotective activity of POLY-MVA against radiation induced damages, Amala Cancer Bulletin, Vol 28, 167-173 6.

Kahn A. “DCA

- Guidelines for clinical use

” Scientific

Presentation. Oncology Association of Naturopathic Physicians Second Annual Meeting. Phoenix, Arizona. February, 2013. 7. Anderson PS. DCA clinical experiences in the BIORC / BCRC NIH trials; 2009-2016.

Abstract:

Research Interests: Integrative Oncology<div>()</div>

Research Interests:
Integrative Oncology